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PLOS One logoLink to PLOS One
. 2023 Apr 13;18(4):e0283326. doi: 10.1371/journal.pone.0283326

Predictors of discharge disposition and mortality following hospitalization with SARS-CoV-2 infection

Farha Ikramuddin 1,*, Tanya Melnik 2, Nicholas E Ingraham 2, Nguyen Nguyen 1, Lianne Siegel 3, Michael G Usher 4, Christopher J Tignanelli 5, Leslie Morse 1
Editor: Robert Jeenchen Chen6
PMCID: PMC10101512  PMID: 37053224

Abstract

Importance

The SARS-CoV-2 pandemic has overwhelmed hospital capacity, prioritizing the need to understand factors associated with type of discharge disposition.

Objective

Characterization of disposition associated factors following SARS-CoV-2.

Design

Retrospective study of SARS-CoV-2 positive patients from March 7th, 2020, to May 4th, 2022, requiring hospitalization.

Setting

Midwest academic health-system.

Participants

Patients above the age 18 years admitted with PCR + SARS-CoV-2.

Intervention

None.

Main outcomes

Discharge to home versus PAC (inpatient rehabilitation facility (IRF), skilled-nursing facility (SNF), long-term acute care (LTACH)), or died/hospice while hospitalized (DH).

Results

We identified 62,279 SARS-CoV-2 PCR+ patients; 6,248 required hospitalizations, of whom 4611(73.8%) were discharged home, 985 (15.8%) to PAC and 652 (10.4%) died in hospital (DH).

Patients discharged to PAC had a higher median age (75.7 years, IQR: 65.6–85.1) compared to those discharged home (57.0 years, IQR: 38.2–69.9), and had longer mean length of stay (LOS) 14.7 days, SD: 14.0) compared to discharge home (5.8 days, SD: 5.9).

Older age (RRR:1.04, 95% CI:1.041–1.055), and higher Elixhauser comorbidity index [EI] (RRR:1.19, 95% CI:1.168–1.218) were associated with higher rate of discharge to PAC versus home. Older age (RRR:1.069, 95% CI:1.060–1.077) and higher EI (RRR:1.09, 95% CI:1.071–1.126) were associated with more frequent DH versus home. Blacks, Asians, and Hispanics were less likely to be discharged to PAC (RRR, 0.64 CI 0.47–0.88), (RRR 0.48 CI 0.34–0.67) and (RRR 0.586 CI 0.352–0.975). Having alpha variant was associated with less frequent PAC discharge versus home (RRR 0.589 CI 0.444–780).

The relative risks for DH were lower with a higher platelet count 0.998 (CI 0.99–0.99) and albumin levels 0.342 (CI 0.26–0.45), and higher with increased CRP (RRR 1.006 CI 1.004–1.007) and D-Dimer (RRR 1.070 CI 1.039–1.101). Increased albumin had lower risk to PAC discharge (RRR 0.630 CI 0.497–0.798. An increase in D-Dimer (RRR1.033 CI 1.002–1.064) and CRP (RRR1.002 CI1.001–1.004) was associated with higher risk of PAC discharge. A breakthrough (BT) infection was associated with lower likelihood of DH and PAC.

Conclusion

Older age, higher EI, CRP and D-Dimer are associated with PAC and DH discharges following hospitalization with COVID-19 infection. BT infection reduces the likelihood of being discharged to PAC and DH.


Question: What factors, both baseline and intrahospital, associate with the need for and type of post-acute discharge following hospitalization for SARS-CoV-2?

Findings: Analysis of this retrospective electronic health record cohort of SARS-CoV-2 patients (n = 6248) hospitalized from March 7th, 2020 –May 4th, 2022, revealed that being older, having higher baseline inflammatory markers, and having more comorbidities increases the likelihood of discharge to a PAC (post-acute care facilities). Discharge to PAC is associated with higher mortality based on state death certificate-based mortality rates. Discharges to PAC are mitigated for patients who develop COVID-19 post vaccination and who have the Alpha variant. Furthermore, Blacks and Asians are more likely to be discharged to home versus PAC.

Meaning: Our findings demonstrated that those admitted with older age and higher comorbidities have increased PAC needs. We find that vaccination is protective to prolonged LOS, ICU stay, number of days in the ICU and death during hospitalization. Patients discharged to PAC have a higher mortality rate on analysis of state death certificate-based mortality rate. Having the alpha variant or a breakthrough infection are more associated with a home discharge than PAC or to die in hospital respectively. Finally, Blacks and Asians are more likely to be discharged home when controlling for other baseline factors, a finding that warrants further study. Of the baseline COVID-19 symptoms obtained from natural language processing, only dyspnea was found to impact disposition by reducing the association of PAC utilization.

Introduction

As of May 22nd, 2022, 90 million individuals have tested positive for SARS-CoV-2 and more than one million deaths have resulted from SARS-COV-2 in the US alone [1,2]. When severe, SARS-COV-2 is associated with a prolonged hospitalization, increased ICU stay and the need for mechanical ventilation [3]. Within 3 months from the start of the pandemic, reports emerged that patients hospitalized with SARS CoV-2 infection were developing impaired physical function thus driving the need for inpatient post-acute care (PAC) facilities which include the inpatient rehabilitation facility(IRF), skilled nursing facilities (SNF) and long term acute care hospitals (LTACH) [4]. Extrapolating from the sepsis literature, functional deficits after infection stem from multiple factors including prolonged hospitalization, ICU stay, intubation, use of steroids, and other systemic complications [5]. As also observed in sepsis, critical illness myopathies, and debility following prolonged intubation, ICU stays, and hospitalization add to the burden of care thus making discharge to home from the hospital challenging [69]. Neurological complications also add to the physical burden and subsequent PAC needs in the SARS-CoV-2 patients population [10]. Cryptogenic stroke has been noted to be twice as common in SARS-COV-2 patients. Encephalopathy and peripheral neuropathies compound these impairments.7 In one study, half of the hospitalized SARS-COV-2 patients were found to have severe impairments in function and performance in activities of daily living [4]. The long-term comorbidities and functional impairment may lead to need for PAC [11].

There are limited data on the outcomes of the inpatient SARS-COV-2 patients following discharge from the acute care hospitals. Given the functional decline seen in these patient population on hospitalization, rehabilitation and discharge disposition is an important pathway to quality of life and return to work. Historically, discharge disposition has been associated with functional status at the time of discharge from the hospital and functional status at discharge is strongly associated with readmission rate [12,13].

A previous study, conducted prior to the general availability of vaccination, analyzed clinical characteristics of SARS-CoV-2 patients admitted to the hospital. The authors observed higher morbidity and mortality in patients with older age, male gender, Hispanic ethnicity, and those with bacterial co-infections and chronic comorbidities [14]. However, there is paucity of studies addressing the predictors of discharge disposition following hospitalization and specifically the PAC needs of the COVID-19 population. In the early part of the pandemic, many factors impacted discharge disposition, including the continued need for isolation on discharge to home, lack of a support system, reduced access to outpatient dialysis (as many dialysis centers did not accept SARS-CoV-2 patients), local healthcare culture, and payor practices and the availability of rehabilitation facilities. As the pandemic evolved, these factors and specifically the rehabilitation needs of this patient population became more pronounced.

With the continued emergence of new and often highly contagious SARS-CoV2 variants, healthcare systems already strapped with reduced staffing continue to be challenged with waxing and waning hospitalization rates [15].

Vaccines have been found to decrease the transmission of breakthrough infections, 40–50% following a single dose and 70% after full vaccination in a studies from the UK [16] and the Netherlands [17]. While vaccination is noted to reduce the rate of hospitalization [18], discharge disposition and rehabilitation needs based on variants and immunization status has not been studied.

Changes in health care policy with the goal to increase patient access, an aging population, coupled with challenging staffing ratios and burnout even preceding the pandemic have most likely contributed to the healthcare staffing shortages impacting inpatient and post-acute care. Recognition of factors associated with utilization of PAC following discharge from the hospitals is of interest to all members of the health care team. Further characterization of factors driving PAC needs requires consideration of new virus variants; the emergence of (breakthrough) infections after vaccination is also of immense interest. We report our analysis of a large database of SARS-COV-2 patients to assess baseline factors associated with discharge disposition from the acute care setting.

Methods

Data collection

Data were abstracted from electronic health records (EHR) reports from a single academic health care system composed of 12 US Midwest hospitals and 60 primary clinics across Minnesota.

The study was approved by all hospitals within the M Health Fairview system which includes ethical approval by the University of Minnesota institutional board. All patients have the option to opt out of research upon establishing care within the MHealth Fairview healthcare system. Data were pooled across different EHRs utilizing a unique patient identifier to account for health care encounters across systems. This study was approved by the University of Minnesota institutional review board (STUDY00001489) which provided a waiver of consent for this study and demographics since March 29th, 1997, and was approved by all hospitals within the M Health Fairview system. State death certificates were linked to the database and enabled accurate out-of-hospital death data for each patient.

Participants

Patients testing PCR positive for the SARS-CoV-2 (SARS- CoV-2 group) during the period of March 7th, 2020, to May 4th, 2022, were included, (Fig 1). We also chose to include patients admitted with a primary diagnosis of influenza from January 6, 2011, to November 14, 2020, as a control group. We could not to include the influenza patients during the pandemic as that specific data was lacking after November 2020.

Fig 1. Study flow chart.

Fig 1

Panel depicts participants agreeing to research selected from the electronic medical record. 62,279 PCR positive patients presented to the hospital systems, 6248 admitted to the hospital were analyzed for discharge disposition of PAC: Post-acute care, IRF: Inpatient rehabilitation unit, SNF: Skilled nursing home, LTACH: Long term care unit.

Both the SARS- CoV-2 group and the influenza group consisted of patients requiring hospital admission to one of the 12 hospitals included in the database and who had a specified discharge disposition.

Variables were selected a priori based on their reported association with SARS-COV-2 morbidity, mortality, known pathophysiology in previous literature. Variables included age, race, gender, BMI, hemoglobin, white blood cell count, platelet count, preadmission albumin, blood type, Rh positive, CRP, Tumor necrosis factor TNF, D Dimer, troponin, hospital length of stay LOS, admission to ICU, ICU LOS, Elixhauser comorbidity index (EI)15 and comorbidities. The data also included those who received Remdesivir, dexamethasone, and tocilizumab.

We combined the analysis of patients who died in hospital with those who were placed into hospice. The died in the hospital/hospice end point is a dependent composite endpoint and will from here be referred to as ‘died in hospital (DH)’. ‘Mortality’ was any death that occurred following discharge from the hospital/PAC outside the hospital/facilities based on state certificate data.

Additional outcomes included the need for extracorporeal membrane oxygenation ECMO.

We categorized discharge disposition to post-acute care (PAC) facilities as a group in addition to describing the discharge dispositions within the PAC group. The post-acute care (PAC) group included inpatient rehabilitation facility (IRF), skilled nursing facility (SNF), and long-term hospital (LTACH).

The variants were based on the timeline of the variants from the GISAID Database (https://covariants.org/per-country?region=World). The dates for the Epsilon variant were Sep 9th, 2020- Mar 8th, 2021, Alpha Variant; Mar 8th, 2021- Jun 14th, 2021, Delta Variant was Jun21st 2021- Dec13th 2021, and Omicron Variant was Dec 13th, 2021, to present [19]. Earlier variants included Epsilon and Robin1.

The main vaccines used in our population were Pfizer-BioNTech, Moderna Bivalent, and Johnson and Johnson’s Janssen vaccines.

Patients were included in the database as vaccinated if they were vaccinated at least with one dose and developed COVID-19 after 2 weeks of being vaccinated. The timeline of two weeks was considered needed to develop immunity against COVID-19 infection.

Statistical analysis

Continuous variables nonparametric variables were compared across the groups using a Mann Whitney test or Kruskal-Wallis test and expressed as median and interquartile range (IQR). Parametric continuous variables were reported as mean and standard deviation. Categorical variables were summarized using counts and percentages and compared across the groups using a Pearson chi-squared test or Fisher’s exact test. Post hoc analysis to determine pairwise differences following the Kruskal Wallis test was carried out using the Dunn’s test. Fisher’s exact test was used to compare presenting symptoms across the discharge disposition. Two- sided p-values less than 0.05 were considered statistically significant.

The overall missingness rate of independent variables included in the primary analysis was 18.2%. The variables were selected based on a model a priori Missingness was addressed using multiple imputation by chained equations; a total of 10 imputed datasets were created.

A regression model was created to compare factors which were significantly associated with discharge to PAC versus home. Descriptive analysis of the patients admitted was completed to study the characteristics. Logistic regression was used for binary variables. Linear regression was used for continuous variables using the auxiliary variable that contained data for the minimum oxygen saturation for the first 24 hours. All analysis was conducted using Stata version 17.0 (Stata Corp, College Station, TX).

Results

A total of 62,279 PCR positive SARS-CoV2 patients presented to the healthcare system between March 7th, 2020, and May 4th,2022. 6248 (10.0%) were admitted to the hospital with a documented discharge disposition. 95.04% of these patients were admitted from home through the emergency department (ED) or outpatient clinics, and 3.6% were from SNF. The remainder 1.46% had been transferred from hospitals outside the healthcare system.

On analysis of discharge disposition, 4611(73.8%) were discharged home, 985 (15.8%) to PAC and 652 (10.4%) died while being hospitalized (DH). The PAC group included 125 (2.06%) discharged to IRF, 801 (13.4%) to SNF and 59 (0.8%) to LTACH.

Characteristics of the SARS-CoV-2 patient by discharge disposition: (Table 1)

Table 1. Demographics and characteristics of patients admitted with COVID-19 based on discharge disposition.

Categorical variables expressed as count and percentage, and continuous variables as median and IQR.

Home Post-Acute Care Hospice/Expired p-value
N 4,611 985 N = 652
Age 57.0 (38.2–69.9) 75.7 (65.6–85.1) 78.1 (66.9–85.6) <0.001
Breakthrough NO 4,259 (92.4%) 914 (92.8%) 620 (95.1%)  0.043
YES 352 (7.6%) 71 (7.2%) 32 (4.9%)
Race White 2,798 (63.1%) 764 (83.1%) 448 (72.6%) <0.001
Black 564 (12.7%) 63 (6.9%) 52 (8.4%)
Asian 527 (11.9%) 49 (5.3%) 77 (12.5%)
Hispanic 349 (7.9%) 19 (2.1%) 21 (3.4%)
Declined 108 (2.4%) 14 (1.5%) 7 (1.1%)
Other 85 (1.9%) 10 (1.1%) 12 (1.9%)
Male 2,161 (46.9%) 477 (48.4%) 353 (54.1%)  0.002
BMI 29.9 (25.7–35.3) 28.7 (24.2–33.7) 28.0 (23.8–32.5) <0.001
Hemoglobin >15.7 g/dl high 141 (3.5%) 23 (2.5%) 20 (3.3%) <0.001
<11.7 g/dl low 1,438 (35.9%) 419 (46.0%) 284 (47.2%)
11.7–15.7 g/dl normal 2,430 (60.6%) 468 (51.4%) 298 (49.5%)
WBC >11/ul high 496 (16.1%) 157 (20.6%) 111 (24.6%) <0.001
>4/ul low 232 (7.5%) 38 (5.0%) 27 (6.0%)
4-11/ul normal 2,350 (76.3%) 566 (74.4%) 314 (69.5%)
Platelets >450/ul high 78 (2.0%) 10 (1.1%) 10 (1.7%) <0.001
<150/ul low 846 (21.8%) 272 (29.7%) 206 (34.3%)
150-450/ul normal 2,952 (76.2%) 633 (69.2%) 385 (64.1%)
Albumin 2.9 (2.5–3.2) 2.7 (2.3–3.0) 2.5 (2.2–2.8) <0.001
Blood type O 1,141 (40.6%) 267 (39.3%) 183 (41.5%)  0.95
A 1,100 (39.2%) 277 (40.7%) 168 (38.1%)
B 431 (15.3%) 99 (14.6%) 67 (15.2%)
AB 136 (4.8%) 37 (5.4%) 23 (5.2%)
Rh pos 2,526 (90.0%) 600 (88.2%) 388 (88.0%)  0.24
CRP 67.0 (29.0–119.0) 73.0 (32.0–129.0) 117.0 (63.5–176.0) <0.001
TNF 22.9 (18.5–32.5) 25.0 (19.3–33.9) 32.2 (21.7–41.8) <0.001
D-DIMER 1.0 (0.6–1.7) 1.3 (0.7–2.4) 1.8 (1.1–3.7) <0.001
Troponin 1.1 (13.0) 0.6 (5.6) 4.0 (56.5)  0.057
Inpatient LOS 5.8 (5.9) 14.7 (14.0) 13.3 (11.3) <0.001
ICU 834 (18.1%) 343 (34.8%) 433 (66.4%) <0.001
ICU LOS 1.1 (6.2) 6.0 (13.0) 9.1 (17.6) <0.001
ECMO 5 (0.1%) 6 (0.6%) 10 (1.5%) <0.001
Remdesivir 2,240 (49.0%) 522 (53.8%) 383 (59.1%) <0.001
Dexamethasone 2,273 (91.4%) 517 (88.5%) 428 (89.2%)  0.046
tocilizumab 162 (3.5%) 68 (6.9%) 77 (11.8%) <0.001
EI 4.0 (2.0–8.0) 9.0 (7.0–12.0) 8.0 (6.0–11.0) <0.001
Mortality 184 (4.0%) 150 (15.2%) 604 (92.6%) <0.001

PAC: Post-Acute Care includes the intense rehabilitation facility, Skilled nursing facility and long-term acute care unit.

Table 1 compares the baseline demographic and inpatient characteristics of SARS-COV-2 patients across discharge dispositions. The median age (IQR) of patients discharged to PAC was 75.7 years (65.6–85.1) compared to 57.0 years among those discharged home (38.2–69.9). Those in the DH group were the oldest 78.1 (66.9–85.6). Lower median albumin levels (IQR) on admission were observed in those discharged to PAC 2.7 (2.3–3.0) gm/dl and DH 2.5 (2.2–2.8) gm/dl compared to those discharged home 2.9 (2.3–3.0) gm/dl. Inflammatory biomarkers and markers of coagulation were analyzed; the normal ranges of these laboratory values are found in S1 Table. Higher median (IQR) CRP, and D-Dimer levels on admission were seen in patients DH: CRP 117.0 (63.5–176.0) mg/dl, D-Dimer 1.8 (1.1–3.7), and discharged to PAC: CRP 73 (32.0–129.0) mg/dl, and D-Dimer 1.3 (0.7–2.4), compared to those discharged to home: CRP 67.0 (29.0–119.0) mg/dl, D-Dimer 1.0 (0.6–1.7). Patients who were discharged to PAC and those who DH had a longer mean (SD) hospital length of stay LOS 14.7 (14.0) days and 13.3 (11.3) days compared to those discharged home 5.8 (5.9) days. More frequent ICU admission, longer ICU LOS, and more frequent ECMO utilization were observed in those in the DH group. Patients having PAC discharges had been admitted to the ICU more frequently than those discharged home (34.8% versus 18.1%, p<0.001). Additionally, patients who had been discharged to PAC had a longer mean ICU stay (6.0 days, SD: 13) compared to those who were discharged home (1.1 days, SD: 6.2, p<0.001). The mortality rate based on state death certificates was 4% for those discharged home, and 15.2% in those discharged to PAC (p<0.001). Those who had been discharged home had a lower median Elixhauser comorbidity index (4.0, IQR: 2.0–8.0), compared to those who were discharged to PAC (9.0, IQR: 7.0–12.0, p<0.001).

Discharge disposition based on variants: (Table 2)

Table 2. Descriptive Table of characteristics and demographics of COVID-19 inpatient based on variants.

Categorical variables expressed as count and percentage, and continuous variables as median and IQR.

Total Early Alpha Delta Omicron p-value
N = 6,248 N = 4,729 (75%) N = 1,105 (17.6%) N = 245 (4.0%) N = 169 (2.7%)
Age 62.4 (44.7–75.6) 64.6 (47.8–77.4) 55.6 (38.5–67.5) 57.5 (42.1–70.1) 59.6 (38.9–74.8) <0.001
Race White 4,010 (67.2%) 2,960 (65.5%) 749 (71.6%) 179 (74.6%) 122 (73.9%) <0.001
Black 679 (11.4%) 523 (11.6%) 119 (11.4%) 25 (10.4%) 12 (7.3%)
Asian 653 (10.9%) 569 (12.6%) 66 (6.3%) 7 (2.9%) 11 (6.7%)
Hispanic 389 (6.5%) 296 (6.6%) 64 (6.1%) 18 (7.5%) 11 (6.7%)
Declined 129 (2.2%) 90 (2.0%) 27 (2.6%) 7 (2.9%) 5 (3.0%)
Other 107 (1.8%) 78 (1.7%) 21 (2.0%) 4 (1.7%) 4 (2.4%)
Male 2,991 (47.9%) 2,263 (47.9%) 525 (47.5%) 122 (49.8%) 81 (47.9%)  0.94
BMI 29.5 (25.1–34.8) 29.3 (25.0–34.4) 30.5 (26.3–36.2) 30.1 (25.8–37.5) 28.5 (25.1–34.9) <0.001
Hemoglobin >15.7 g/dl high 184 (3.3%) 137 (3.3%) 39 (4.0%) 4 (1.8%) 4 (2.6%) <0.001
<11.7 g/dl low 2,141 (38.8%) 1,657 (39.7%) 336 (34.8%) 72 (32.0%) 76 (49.7%)
11.7–15.7 g/dl normal 3,196 (57.9%) 2,383 (57.1%) 591 (61.2%) 149 (66.2%) 73 (47.7%)
WBC >11/ul high 764 (17.8%) 515 (16.8%) 220 (20.6%) 12 (16.7%) 17 (20.2%) <0.001
>4/ul low 297 (6.9%) 161 (5.2%) 118 (11.0%) 8 (11.1%) 10 (11.9%)
4-11/dl normal 3,230 (75.3%) 2,391 (78.0%) 730 (68.4%) 52 (72.2%) 57 (67.9%)
Platelets >450/dl high 98 (1.8%) 69 (1.7%) 19 (2.0%) 8 (3.6%) 2 (1.4%)  0.36
<150/dl low 1,324 (24.6%) 1,016 (24.9%) 227 (24.1%) 51 (22.9%) 30 (20.4%)
150–450 /ul normal 3,970 (73.6%) 2,997 (73.4%) 694 (73.8%) 164 (73.5%) 115 (78.2%)
Albumin 2.8 (2.5–3.1) 2.8 (2.5–3.1) 2.8 (2.5–3.1) 2.7 (2.4–2.9) 2.8 (2.5–3.1) <0.001
Blood type O 1,591 (40.5%) 1,228 (40.4%) 258 (38.8%) 67 (46.9%) 38 (46.9%)  0.23
A 1,545 (39.3%) 1,179 (38.8%) 283 (42.6%) 56 (39.2%) 27 (33.3%)
B 597 (15.2%) 477 (15.7%) 93 (14.0%) 13 (9.1%) 14 (17.3%)
AB 196 (5.0%) 156 (5.1%) 31 (4.7%) 7 (4.9%) 2 (2.5%)
Rh pos 3,514 (89.4%) 2,733 (89.9%) 588 (88.4%) 122 (85.3%) 71 (87.7%)  0.23
CRP 72.4 (32.7–128.0) 73.0 (32.4–130.0) 70.3 (33.0–119.0) 76.5 (42.3–117.5) 69.8 (19.0–130.0)  0.35
TNF 24.3 (18.8–34.8) 24.0 (18.8–34.3) 29.9 (20.9–47.0) 28.1 (28.1–28.1)  0.63
DDIMER 48h 1.1 (0.6–2.1) 1.1 (0.6–2.2) 1.0 (0.6–1.9) 1.1 (0.6–1.8) 0.9 (0.6–2.3)  0.46
Troponin 1.4 (23.5) 0.5 (4.9) 0.8 (9.2) 12.7 (58.4) 52.8 (189.1) <0.001
Inpatient LOS 8.0 (9.1) 8.2 (9.1) 6.9 (8.6) 9.2 (11.5) 6.9 (8.4) <0.001
ICU 1,610 (25.8%) 1,282 (27.1%) 247 (22.4%) 55 (22.4%) 26 (15.4%) <0.001
ICU_Days 2.7 (9.8) 2.8 (10.6) 2.1 (6.1) 3.3 (9.2) 1.3 (6.2)  0.021
ECMO 21 (0.3%) 13 (0.3%) 7 (0.6%) 0 (0.0%) 1 (0.6%)  0.20
Remdesivir 3,145 (50.8%) 2,264 (48.4%) 660 (60.3%) 155 (63.5%) 66 (39.8%) <0.001
Dexamethasone 3,218 (90.6%) 2,315 (89.9%) 658 (93.7%) 167 (97.1%) 78 (77.2%) <0.001
tocilizumab 307 (4.9%) 131 (2.8%) 122 (11.0%) 46 (18.8%) 8 (4.7%) <0.001
EI 6.0 (3.0–9.0) 6.0 (3.0–10.0) 5.0 (2.0–8.0) 5.0 (3.0–8.0) 6.0 (3.0–10.0) <0.001
Breakthrough 455 (7.3%) 66 (1.4%) 225 (20.4%) 70 (28.6%) 94 (55.6%) <0.001
Mortality 938 (15.0%) 796 (16.8%) 110 (10.0%) 22 (9.0%) 10 (5.9%) <0.001

Variants were determined based on the timeline from the GISAID (https://covariants.org/per-country?region=World). The in-hospital mortality was the highest with the early variants at 16.8%, 10% in patients with alpha variant, 9.0% in the delta and 5.9% in omicron population. In our analysis, 55% of the Omicron patients were breakthrough (BT) infections, 28.6% in the delta variants were BT, and 20.4% in alpha. The mean inpatient LOS was the highest in patients with delta variant (9.2 days SD: 11.5), and shortest in patients with the alpha (6.9 days, SD: 8.6) and omicron (6.9 days, SD: 8.4) variants. Increased PAC needs were associated with older age, and higher EI score. Higher albumin level, and breakthrough infection were associated with discharge home following hospitalization. See Table 2 for descriptive analysis of the discharge disposition based on variants.

Baseline characteristics of vaccinated versus non-vaccinated: (see Table 3)

Table 3. Comparison of vaccinated and non-vaccinated SARS-CoV-2 patients admitted to hospital.

Categorical variables expressed as count and percentage, and continuous variables as median and IQR.

Total Non-Vaccinated Vaccinated p-value
N = 6,248 N = 5,793 N = 455
Age 62.4 (44.7–75.6) 62.0 (44.1–75.2) 67.5 (54.8–79.0) <0.001
Race White 4,010 (67.2%) 3,660 (66.1%) 350 (81.2%) <0.001
Black 679 (11.4%) 650 (11.7%) 29 (6.7%)
Asian 653 (10.9%) 632 (11.4%) 21 (4.9%)
Hispanic 389 (6.5%) 372 (6.7%) 17 (3.9%)
Declined 129 (2.2%) 119 (2.1%) 10 (2.3%)
Other 107 (1.8%) 103 (1.9%) 4 (0.9%)
Male 2,991 (47.9%) 2,756 (47.6%) 235 (51.6%)  0.094
BMI 29.5 (25.1–34.8) 29.5 (25.1–34.8) 29.0 (24.8–34.2)  0.41
Hemoglobin >15.7 g/dl high 184 (3.3%) 177 (3.5%) 7 (1.7%) <0.001
<11.7 g/dl low 2,141 (38.8%) 1,938 (38.0%) 203 (48.4%)
11.7–15.7 g/dl normal 3,196 (57.9%) 2,987 (58.5%) 209 (49.9%)
WBC >11/ul high 764 (17.8%) 689 (17.6%) 75 (19.9%)  0.013
>4/ul low 297 (6.9%) 259 (6.6%) 38 (10.1%)
4-11/ul normal 3,230 (75.3%) 2,967 (75.8%) 263 (69.9%)
Platelets >450/ul high 98 (1.8%) 90 (1.8%) 8 (1.9%)  0.94
>150/ul low 1,324 (24.6%) 1,220 (24.5%) 104 (25.1%)
150-450/ul normal 3,970 (73.6%) 3,668 (73.7%) 302 (72.9%)
Albumin 2.8 (2.5–3.1) 2.8 (2.5–3.1) 2.8 (2.5–3.1)  0.75
Blood type O 1,591 (40.5%) 1,481 (40.5%) 110 (40.1%)  0.094
A 1,545 (39.3%) 1,422 (38.9%) 123 (44.9%)
B 597 (15.2%) 567 (15.5%) 30 (10.9%)
AB 196 (5.0%) 185 (5.1%) 11 (4.0%)
Rh pos 3,514 (89.4%) 3,275 (89.6%) 239 (87.2%)  0.22
CRP 72.4 (32.7–128.0) 72.0 (33.0–128.0) 74.5 (32.0–133.0)  0.72
TNF 24.3 (18.8–34.8) 24.5 (18.8–34.8) 20.9 (20.9–20.9)  0.63
D DIMER 1.1 (0.6–2.1) 1.1 (0.6–2.1) 1.0 (0.6–2.1)  0.62
Troponin 1.4 (23.5) 1.3 (24.0) 2.8 (9.6)  0.47
Inpatient LOS 8.0 (9.1) 8.0 (9.2) 7.1 (8.6)  0.029
No/% in ICU 1,610 (25.8%) 1,528 (26.4%) 82 (18.0%) <0.001
ICU Days 2.7 (9.8) 2.8 (10.0) 1.6 (6.0)  0.016
ECMO 21 (0.3%) 20 (0.3%) 1 (0.2%)  0.66
Remdesivir 3,145 (50.8%) 2,933 (51.1%) 212 (47.1%)  0.10
Dexamethasone 3,218 (90.6%) 2,974 (90.7%) 244 (90.4%)  0.87
Tocilizumab 307 (4.9%) 281 (4.9%) 26 (5.7%)  0.41
EI 6.0 (3.0–9.0) 6.0 (3.0–9.0) 7.0 (4.0–11.0) <0.001
Mortality 938 (15.0%) 880 (15.2%) 58 (12.7%)  0.16

The median age of patients with breakthrough infections (67.5 years, IQR: 54.8–79.0) was older than that of those who were non-vaccinated (62.0 years, IQR: 44.1–75.2). Those with BT infection were less often admitted to the ICU (18%) compared to the non-vaccinated patients (26.4%, p<0.001). Those with BT had a higher median EI (7.0, IQR: 4.0–11.0), compared to those who were not vaccinated (6.0, IQR: 3.0–9.0) (see Table 3).

Association of factors to discharge disposition

A multinomial model was constructed to explore the association between hospital discharge disposition and the following baseline factors known to impact outcomes from SARS-CoV-2 infection (see Table 4). We first performed a multinomial logistic regression analysis of complete cases (i.e., only patients with complete data) with the outcome variables being home (baseline category), PAC and DH. We included the following variables: age, gender, having a breakthrough(BT) infection, virus variant (as determined as the dominant type at the time of having a PCR positive test), race/ethnicity (White, Asian, Black, Hispanic), BMI, COVID-19 symptoms at the time of presentation (fatigue, shortness of breath, fever, and palpitations), the Elixhauser Comorbidity Index (EI) and laboratory studies including white blood cell count (WBC) count, D-Dimer, CRP, platelet count and albumin. For laboratory studies we used the first available value within three days of admission. Prior to multiple imputation of missing variables, the model was statistically valid with an F statistic < 0.0001. Imputations were performed for each of the variables included in the above model except for age, race, and BMI. Imputation was performed using the auxiliary variable that contained data for the minimum oxygen saturation for the first 24 hours. A Stata postestimation command to test goodness of fit for a multinomial logistic regression model showed no difference between the observed and expected frequencies within 10 groups. We then generated areas under the curve to determine the classification accuracy of the logistical regression model to generate multiclass ROC curves for classification accuracy based on multinomial logistic regression using yielding an AUROC of 0.789.

Table 4. Multinomial logistic regression of discharge dispositions i.e., post-acute care or died in hospital with the base outcome for comparison being home.

Post-acute care
RRR P value 95% Confidence Interval
Age 1.048 0 1.04 1.05
Variant
Alpha 0.58 0 0.44 0.78
Delta 0.64 0.08 0.38 1.05
Omicron 0.63 0.13 0.34 1.15
Breakthrough 0.67 0.03 0.47 0.97
Race
Black 0.64 0.006 0.47 0.88
Asian 0.48 0 0.34 0.67
Hispanic 0.61 0.06 0.37 1.02
BMI 0.99 0.26 0.98 1
Male 0.94 0.51 0.79 1.12
Dyspnea 0.66 0 0.55 0.8
Fatigue 1.12 0.17 0.94 1.34
Fever 1.14 0.18 0.93 1.38
Palpitations 1.12 0.17 0.94 1.34
Adm WBC 1.01 0.06 0.99 1.02
Hemoglobin 1.04 0.112 0.99 1.09
Platelet 1 0.34 0.99 1
Albumin 0.55 0 0.43 0.69
EI 1.19 0 1.16 1.21
Died in hospital
Age 1.06 0 1.06 1.07
Variant
Alpha 0.87 0.4 0.64 1.19
Delta 0.84 0.56 0.47 1.49
Omicron 0.63 0.27 0.28 1.43
Breakthrough 0.42 0 0.26 0.68
Race
Black 1.03 0.83 0.73 1.47
Asian 1.31 0.08 0.96 1.79
Hispanic 1.14 0.6 0.68 1.91
BMI 0.99 0.19 0.97 1
Male 1.29 0.01 1.06 1.58
Dyspnea 1.37 0.009 1.08 1.75
Fatigue 0.82 0.06 0.66 1.01
Fever 0.95 0.7 0.77 1.18
Palpitations 1.17 0.12 0.95 1.45
Adm WBC 1.01 0.01 1 1.03
Hemoglobin 1.01 0.66 0.95 1.07
Platelet 0.99 0 0.99 0.99
Albumin 0.34 0 0.26 0.45
EI 1.09 0 1.07 1.12

Older age (RRR: 1.04, 95% CI: 1.041–1.055), and higher EI (RRR:1.19, 95% CI: 1.17–1.22) were associated with a higher rate of discharge to PAC versus home. Similarly, older age (RRR:1.07, 1.06–1.07) and higher EI (RRR:1.09, 95% CI: 1.07–1.13) were associated with higher rates of DH versus home. Blacks (RRR: 0.64, 95% CI: 0.47–0.88), Asians (RRR: 0.48, 95% CI: 0.34–0.67) and Hispanics (RRR: 0.58, 95% CI: 0.35–0.97) were less likely to receive PAC, compared to white patients (see Table 4).

Among COVID-19 symptoms, dyspnea on presentation was significantly associated with less frequent discharge to PAC (RRR: 0.66, 95% CI: 0.55-.80) compared to home, but was not associated with more frequent DH (RRR: 1.2, 95% CI: 0.98–1.59). No other symptoms at presentation were significantly associated with discharge status (Table 5 if accepted, production will need this reference to link the reader to the Table).

Table 5. Analysis of discharge disposition based on symptom at presentation.

Categorical variables expressed as percent.

Total Home IRF SNF LTACH Hospice/Expired p-value
N = 6,248 N = 4,611 N = 125 N = 801 N = 59 N = 652
General aches 5.1%  5.1%  2.0%  3.8%  10.0%  6.7%   0.057
Sore Throat 3.4%  3.5%  2.0%  3.6%  2.5%  2.7%   0.79
Rhinorrhea 4.9%  4.7%  3.1%  5.7%  2.5%  5.4%   0.63
Nausea/Vomiting 9.6%  9.1%  5.1%  12.9%  7.5%  10.5%   0.011
Diarrhea 7.1%  6.7%  6.1%  8.0%  5.0%  8.6%   0.41
Fatigue 12.0%  10.4%  13.3%  17.2%  12.5%  16.2%  <0.001
Dyspnea 14.9%  13.5%  12.2%  17.4%  12.5%  22.5%  <0.001
Cough 15.8%  14.5%  19.4%  19.6%  12.5%  19.3%  <0.001
Joint pain 3.7%  3.2%  6.1%  5.4%  2.5%  5.0%   0.013
Chest Pain 6.0%  5.9%  3.1%  6.7%  5.0%  6.7%   0.62
Brain fog 0.0%  0.0%  0.0%  0.0%  0.0%  0.0%   0.99
Depression 5.0%  4.6%  4.1%  6.1%  5.0%  6.5%   0.19
Muscle pain 3.8%  3.9%  2.0%  1.9%  10.0%  5.6%   0.002
HA 8.6%  8.4%  9.2%  9.7%  2.5%  8.8%   0.52
Fever 13.9%  13.0%  15.3%  15.8%  12.5%  17.5%   0.027
Palpitation 11.8%  10.6%  7.1%  15.3%  15.0%  16.8%  <0.001
Rash 4.7%  4.5%  2.0%  4.9%  5.0%  6.1%   0.32
Hair loss 0.2%  0.2%  0.0%  0.1%  0.0%  0.2%   0.99
Loss of smell/taste 1.6%  2.0%  0.0%  0.9%  0.0%  0.4%   0.009
Insomnia 1.9%  1.4%  2.0%  4.2%  2.5%  2.3%  <0.001
Difficulty Thinking 0.1%  0.1%  0.0%  0.3%  0.0%  0.0%   0.29
Difficulty Memory 1.1%  0.4%  0.0%  4.4%  0.0%  2.5%  <0.001
Anxiety 3.4%  3.4%  2.0%  3.9%  2.5%  2.9%   0.79

Relative to early strains, having the alpha variant was associated with less frequent PAC discharge versus home (RRR 0.59 CI 0.44–0.78) but viral strain was not associated with the risk of DH compared to discharge home. The risk for discharge to PAC (RRR: 0.68, CI: 0.47–0.98) and DH (RRR 0.43, CI: 0.26–0.68) compared to home was lower for those participants presenting with BT infections.

For laboratory studies including the inflammatory markers, for every 1 mg/dl increase in albumin the relative risk of discharge to DH is reduced by 0.34 versus home (RRR: 0.34, CI: 0.26–0.45). Similarly, every unit increase in platelet count (RRR: 0.99, CI: 0.99–0.99) was associated with lower risks of 0.99 discharge to DH versus home. Conversely higher CRP (RRR:1.01, CI: 1.00–1.01) and coagulation marker D-Dimer (RRR: 1.07, CI: 1.04–1.10) were both associated with an increased risks of DH relative to going home. WBC was not significantly associated with higher rates of any discharge disposition. Higher hemoglobin (RRR: 1.04, CI: 1.00–1.10), D-Dimer (RRR: 1.03 CI: 1.00–1.06), and CRP (RRR: 1.00, CI:1.01–1.04) were associated with a higher risk of PAC discharge relative to home.

Characteristics of patients comparing the COVID 19 infections to influenza

Compared to influenza patients, the COVID-19 patients had a higher median age (62.4 years, IQR: 44.7–75.6 versus 47.8 years, IQR: 31.3–68.7). The COVID-19 patients had a higher mean EI compared to influenza patients (6.0, IQR: 3.0–9.0 versus 0.0, IQR: 0.0–8.0), p = 0.001). The mortality rate in the COVID-19 group was higher compared to influenza group (9.6% versus 0.8% respectively, p = <0.001). COVID-19 patients had a longer median hospital LOS (5.0, IQR 2.9–9.1 days versus 0.2 IQR: 0.1–1.7). In total, 25.8% of the COVID-19 patients were admitted to the ICU, compared to 3.4% of the influenza patients see Tables 6 and 7 (if accepted, production will need this reference to link the reader to the Table).

Table 6. Descriptive Table: Comparison of the SARS-CoV-2 to influenza patients admitted to hospital.

Categorical variables expressed as count and percent, and continuous variables as median and IQR.

COVID Patients Influenza Patients p-value
N = 6,248 N = 4,370
Age 62.4 (44.7–75.6) 47.8 (31.3–68.7) <0.001
Race White 4,010 (67.2%) 2,810 (64.3%) <0.001
Black 679 (11.4%) 686 (15.7%)
Asian 653 (10.9%) 493 (11.3%)
Hispanic 389 (6.5%) 20 (0.5%)
Declined 129 (2.2%) 93 (2.1%)
Other 107 (1.8%) 266 (6.1%)
Male 2,991 (47.9%) 1,828 (41.8%) <0.001
BMI 29.5 (25.1–34.8) 28.0 (24.1–33.2) <0.001
Hgb on admission 12.4 (11.0–13.8) 13.3 (12.1–14.5) <0.001
WBC on admission 6.4 (4.4–9.1) 7.0 (5.3–9.0) <0.001
Platelet Count on admission 196.0 (149.0–258.0) 187.0 (150.0–231.0) <0.001
Pre-admit Albumin 3.4 (2.8–3.8) 3.7 (3.4–4.1) <0.001
Inpatient LOS 5.0 (2.9–9.1) 0.2 (0.1–1.7) <0.001
ICU 1,610 (25.8%) 149 (3.4%) <0.001
COPD 1,051 (16.9%) 348 (12.6%) <0.001
CVD 1,122 (18.1%) 311 (11.3%) <0.001
Heart Txp 24 (0.4%) 4 (0.1%)  0.058
Kidney Txp 134 (2.2%) 22 (0.8%) <0.001
Liver Txp 40 (0.6%) 12 (0.4%)  0.23
Lung Txp 25 (0.4%) 2 (0.1%)  0.008
Sleep Apnea 1,331 (21.4%) 352 (12.7%) <0.001
T2DM 2,194 (35.3%) 545 (19.7%) <0.001
Hypertension 4,121 (66.3%) 1,240 (44.9%) <0.001
HFpEF 766 (12.3%) 196 (7.1%) <0.001
CAD 1,540 (24.8%) 408 (14.8%) <0.001
Any Liver Disease 1,049 (16.9%) 233 (8.4%) <0.001
EI 6.0 (3.0–9.0) 0.0 (0.0–8.0) <0.001
Mortality 600 (9.6%) 36 (0.8%) <0.001

BMI: Body mass index, Hgb: Hemoglobin, WBC: White count cell, LOS: Length of stay, ICU: Intensive care unit, COPD: Chronic obstructive pulmonary disease, CVD: Cerebrovascular disease, TXP; transplantation, T2DM: Type 2 diabetes mellites, HFpEF: Heart failure with preserved ejection fraction, CAD: Coronary artery disease, EI: Elixhauser comorbidity score.

Table 7. Discharge dispositions of SARS-CoV-2 and influenza inpatient populations.

SARS-COV-2
Patients
Influenza Patients p-value
N = 5,593 N = 4,370
Discharge
disposition
Home 4,098 (73.3%) 4,085 (93.5%) <0.001
Post-Acute Care 905 (16.2%) 258 (5.9%)
Hospice/Expired 590 (10.5%) 25 (0.6%)

Discussion

We sought to determine the relationship between baseline factors including inflammatory markers, and COVID-19 symptoms at presentation and discharge disposition, taking into consideration the variant and vaccine status. Additionally, we hoped to contextualize our findings by comparing the discharge dispositions of patients who had been hospitalized with a primary diagnosis of influenza to determine if there might be any differences in PAC utilization.

In this analysis of 6,248 patients, those of Black, or Asian race or being of Hispanic ethnicity were of increased likelihood to be discharged home than to a PAC when compared to White patients in our study. It has been recognized from previous studies that Blacks and Latinos have increased rates SARS-CoV-2 infection, severity of disease and mortality [20]. However, in our analysis, discharge to PAC was found to be less common for these cohorts. The observation that race is independently associated with discharge home warrants further study of the disparities in access to options in discharge planning. In our analysis, while Blacks and Asians were less likely to be discharged to PAC, they were not more likely to die or be placed in hospice. The data on the incidence and mortality of COVID-19 on minorities is limited but expanding; however, in one report minorities, specifically Blacks in New York City, had a substantially higher mortality in the pandemic [21]. In general, Blacks were noted to have a disproportionate outcome burden in the pandemic [22]. Further studies are needed to understand the barriers to admission to rehabilitation facilities in the minorities. There have been previous studies in stroke populations which have shown that Blacks tend to have a less favorable outcomes if they survive when factoring in the impact of discharge disposition.

Several studies have highlighted the central role of inflammation in COVID-19 population in determining the disease severity and adverse clinical outcomes [23]; however, how these outcomes relate to discharge disposition, rehabilitation needs, and in and out of hospital mortality has not been studied. In this report, baseline CRP and D-Dimer were highest for those in the DH group, followed by PAC and home. In controlling for other factors, higher levels of these inflammatory markers on presentation are associated with dying in the hospital compared to discharge home. Not unexpectedly, patients discharged to PAC had a higher mortality rate compared to those discharged home based on the state death certificates. After controlling for CRP, WBC was not a significant predictor of disposition, but higher platelet counts were associated with lower rates of DH disposition. As newer therapies emerge for the management of SARS-CoV-2 infection, monitoring levels of these inflammatory markers may be a reasonable approach to predict outcomes.

While our primary focus was baseline factors that drive discharge disposition, we found that the patients who were discharged to PAC and DH had a longer inpatient LOS, were more likely to be placed into the ICU, and had a longer ICU stay during hospitalization. These findings were not unexpected considering that patients with a disposition PAC or DH had a higher EI. These values may be helpful in determining algorithms to in hospital care utilization for future surges of COVID-19.

Vaccination against SARS-CoV2 has been associated with mitigation of the severity of infection, and decreased rates of hospitalization [18]. In this analysis, presenting with a BT infection was associated with a lower risk of dying or utilizing PAC. Additionally, participants had a shorter length of hospitalization, were less likely to be transferred to the ICU, and when admitted into the ICU, they had a shorter ICU stay. This is an important consideration given the incomplete penetrance of vaccine uptake in the population. It will be important to assess over time the duration of protection offered by the initial vaccine and subsequent boosters. After controlling for vaccination status, we found that infection with the alpha variant was associated with being less likely to be discharged to PAC relative to home, compared to earlier strains.

A key strength of our study is the large sample size, which includes 62,279 PCR positive SARS-CoV-2 patients who presented to the healthcare system of whom 6248 patients who were admitted and were analyzed. This study offers a focused analysis of the discharge disposition and post-acute care needs of SARS-CoV-2 patients following hospitalization. Mutations and reinfections have been a challenge for the hospital capacity and understanding the PAC needs of the SARS-CoV-2 inpatients is an important factor for expense, planning and disparities. Another strength of the paper is the impact of vaccination on the discharge disposition and longer-term mortality following discharge further supporting planning and resource allocation during the pandemic.

One key limitation of the study is the inability to account for the factors inherent to the pandemic and local practices that determine the discharge disposition to the PAC during the pandemic. We have attempted to compare the SARS-CoV-2 inpatient population with a similar population of patients admitted to hospital with the primary diagnosis of influenza, outside the pandemic dates as a baseline for PAC admissions. The influenza patient database was chosen due to the similarities in disease spread and clinical burden when admitted and had a similar hospital course, with need for ventilation secondary ARDS and effect on multiple organs. However, we recognize that the time course over which influenza patients were admitted was much longer and in a setting of markedly less constraint as experienced during the height of the pandemic and with the continued exodus of nursing staff from the work force. We did not think comparing the SARS-CoV-2 inpatient population to those traditionally admitted to the acute rehabilitation facilities with neurological deficits, traumatic brain injury or spinal cord injury would be a reasonable comparison. A recent study comparing the death rate of influenza and SARS-CoV-2 populations found that the decedents of SARS-CoV-2 were more likely to be male, between the age of 65 and 84 years, and were also more likely to have a higher incidence of a history of diabetes, hypertension, and obesity [24].

At a time of restricted resources and current crunch in labor in the pandemic, additional burden for hospitalization and PAC needs from the influenza patients in the flu season may add challenges to the healthcare system and needs further scrutiny and resource stratification. Appearance of additional variants of SARS-CoV-2 can also intensify the burden. Certainly resources i.e., staffing, and bed availability drive mortality [25], and understanding baseline predictors of patients including common symptoms of SARS-CoV-2 is of immense interest in the setting of constrained staffing models.

Long term morbidity following the prolonged hospitalization and the complications inherent to SARS- CoV-2 admission are not fully understood. While the functional and cognitive deficits that drive the discharges following hospitalization vary, the rehabilitation needs of these patients and a measure of return to baseline has not been quantified and remains ambiguous [26,27]. Furthermore, the impact on disability, quality of life (QoL) and workability remains to be studied. To the best of our knowledge, our study is the first to look at specific discharge dispositions of the SARS-COV-2 patients following hospitalization.

Conclusion

In the setting of universally constrained healthcare staffing, understanding factors associated discharge disposition for patients admitted with COVID-19 remains of paramount importance. In this cohort of 6,248 patients admitted with SARS-CoV-2 infection, we observed that having a later variant and admission vaccination was associated with more favorable outcomes as indicated by discharge disposition. Further, older age, a greater burden of comorbidities, and longer hospital LOS, ICU LOS, and ICU admission are associated with discharge to PAC and dying in the hospital or discharge to hospice. The observation that race and ethnicity is independently associated with discharge home warrants further study of the disparities in discharge planning.

Supporting information

S1 Table. New onset SARS-COV-2 symptoms on presentation by discharge disposition using Fisher’s exact test.

(DOCX)

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

Funding for this study was provided by National Institute of Health's National Center for advancing Translational Sciences Grant U01TR002062, however the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

Decision Letter 0

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7 Apr 2022

PONE-D-21-40001Differences in Discharge Disposition following Hospitalizations for SARS-CoV-2 and influenzaPLOS ONE

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Reviewer #1: In this multicenter retrospective study, the authors describe and compare discharge dispositions following hospitalization among patients infected with SARS-CoV-2 and influenza. The authors find significant differences in the number of patients discharged to post-acute care (PAC) with a higher proportion of SARS-CoV-2 patients discharged to PAC, as well as longer length of hospitalization and higher mortality among patients with SARS-CoV-2. The authors also investigate associations between various clinical and laboratory parameters and discharge to PAC for patients with SARS-CoV-2. The strengths of the study include the large sample size as well as linking of patient data to state death certificates to characterize out of hospital death. My comments regarding this study are summarized below:

Major Comments:

1. Can the authors justify why these laboratory parameters were chosen to be included? Some of the variables such as CRP and albumin are more intuitive as markers of inflammation and nutritional status. Others are less so. For instance, why are blood type and Rh positive include in the analysis?

2. It is challenging to assess the clinical relevance of the differences found in laboratory parameters for hemoglobin, white blood cell count, platelets, etc. (Table 3). Most of the reported medians and interquartile ranges fall within the normal range of values for these variables. The authors could consider presenting these as categorical variables with cut-offs for low, normal, and high values. As it stands, it seems difficult to conclude that differences in WBC, where the medians range from 6 – 8, suggest significantly different states of inflammation.

3. For the multinomial logistic regression, how were variables of interest selected for inclusion in the model? Were these selected a-priori?

4. The rationale for evaluating presenting symptoms and association with discharge disposition is not entirely clear. Do you hypothesize that presenting symptoms may reflect severity of disease at presentation or potential extrapulmonary involvement? For instance, fever or body aches may suggest a more systemic inflammatory response.

5. The authors note that fewer Black and Asian patients are discharged to PACs compared to home. Is there literature regarding racial / ethnic disparities in hospital discharge disposition accounting for severity of illness and co-morbidities? This finding is worth noting in the discussion.

6. Is data available regarding where patients are coming from on hospital admission? (E.g. residing at home vs. SNF). Certainly, early in the pandemic many SNFs had large COVID outbreaks. This may impact the interpretation of results in the sense that some patients may be returning to SNF on discharge.

7. What is the minimum duration of observation between hospital discharge and out-patient death? In other words, were death certificates updated 3 months after the last discharge, 6 months etc.?

Minor Comments:

1. In the introduction, the significance is framed around the current influenza season. Given that the influenza season typically peaks in February or March in the US, the authors should consider updating some of the phrasing here.

2. Why does available data stop in November 2020 for influenza patients? As opposed to June 2021 for SARS-CoV-2 patients.

3. Page 11-12: It appears that there is duplicated text in the methods for the paragraphs starting with “State death certificates were linked”.

4. For clarity throughout the paper, I would suggest specifying that expired refers to in-hospital death throughout the text. Similarly, would clarify what “Mortality” in Table 2 and 3 refers to. Is this combined in and out of hospital death?

5. Table 3 - is there an error in median ICU LOS? Should this be presented as median (IQR) of ICU LOS for patients who were admitted to the ICU in each respective category.

6. Table 3 – There is no p-value for CRP.

7. Please include in the supplement which explanatory variables were excluded due to missingness and which were imputed. Missingness of 44% is quite high.

8. This may be a technical issue, but several of the mentioned supplemental tables and flow chart are not available on my review.

9. There are a few typos in the manuscript – E.g. Page 17 “between the age of 65 and 8418”.

Reviewer #2: Thank you for the opportunity to read your work.

The question asked seems relevant to me: what are the PAC needs for patients with Covid? Can we identify the predictive factors for final discharge to CAP?

Integrating patients with Influenza during other periods/years complicates the work and makes the results less readable. This question seems to me to belong to another study.

Introduction

The issue of SARS-Cov-2 variants is major. We know that the severity of the disease is strongly linked to the identified variant and to the vaccination status of the patient. this should be discussed in the introduction. In your work the variants have not been identified and it seems to me that this may be a major weakness in the work. You should specify the distribution of variants during the study period, and the vaccination rates of the general population and the population at risk of developing severe forms.

Methods

Discharge to PAC is very variable and depends on local practices, the availability of places in these structures, modes of financing, a medical and probably also social culture on the place of the elderly, and the possibilities of maintaining home for these patients.

I think it would have been interesting to describe the usual population (even admitted during the same period of study) admitted to your centers, those transferred to PAC, and describe the predictive factors of transfer.

The choice of influenza, as I can understand, is skewed if you haven't performed routine influenza screening in recent patients admitted for respiratory manifestations.

And the practices and the availability of places and PAC have certainly changed during the period of the study.

A flowchart of the patients included in the study should be presented. The tested, the admitted with SARS-Cov-2 and Influenza virus.

The severity of patients, their previous condition, and their condition at discharge are also variables to be assessed. Differences between centers and between age categories, etc., may also influence the final decision. This is not discussed in your introduction nor in the method.

What means hospice/expired? It is a composite end-point?

Results

I have a little trouble understanding the care pathways: how many came from outpatient facilities and how many were diagnosed and probably immediately serious in the emergency room?

I think we need to reduce the text and better present the results in tables. The flu vs Covid comparisons make it difficult to understand the results.

Patients with SARS Cov 2 are more serious, more often polypathological, and older. Their hospital stay is more favourable, shorter and require less sheave. Can we compare them on the orientations at the exit?

In the prediction model, did you include patients with Influenza? If so, the Covid does not appear as a predictive factor?

Or are it only the identified factors that explain the observed differences?

Discussion

The first paragraph should state the strengths of your work and your main results, your most important messages.

The discussion on mortality (in the general population and in-hospital...), the clinical characteristics and the severity factors of Influenza make it difficult to understand the text.

I don't understand the third paragraph, due to the discussion of PAC needs of flu patients.

The fourth paragraph: I don't think you can really conclude that the bed needs of patients with SARS Cov 2 are higher than those of patients with Influenza. The context and overload of the healthcare system was not the same during the pandemic period as in previous years during periods of seasonal flu.

Logic would have wanted to discuss first the predictive value of CAP of the variables related to the terrain, then the clinical picture, then the biological parameters and clinical characteristics, then the variables related to severity then the variables related to the hospital stay.

A question: the transfer rates were the same in the 12 centers? Did you notice a center effect? This can be important in the discussion of center practices and habits.

You discuss inflammatory markers in Covid, but you haven't assessed C-reative protein, a recognized severity marker in those patients. Could you be more precise?

Conclusion

I am not sure that you can say that the PAC needs of patients admitted for SARS-Cov-2 are higher than those of patients admitted for Influenza.

I don't understand why you say the predictors of discharge to PAC are different...or the presentation in the text and tables is confusing.

Tables

Tables 1 and 2

Table 1 too short with too long presentation of results in Results. Table 1 and 2 should be merged and simplified.

Table 3

These results are very briefly discussed in the discussion. Is it really important to keep them?

Chart 4

This analysis only concerns patients with SARS-Cov-2 or does it include patients with Influenza?

I don't see Covid/influenza in the variables.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2023 Apr 13;18(4):e0283326. doi: 10.1371/journal.pone.0283326.r002

Author response to Decision Letter 0


2 Dec 2022

Thank you for the constructive and important comments made, we are resubmitting the manuscript after major revision. As per your comments, added variants and vaccination status to the analysis.

Attachment

Submitted filename: Response to Review PLOS ONE Final (3).docx

Decision Letter 1

Robert Jeenchen Chen

22 Dec 2022

PONE-D-21-40001R1Predictors of Discharge Disposition and Mortality following Hospitalization with SARS-CoV-2 InfectionPLOS ONE

Dear Dr. IKRAMUDDIN,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please revise.

Please submit your revised manuscript by Feb 05 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: (No Response)

Reviewer #4: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

Reviewer #4: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: This submission by Ikramuddin et al performed retrospective analysis on a cohort of 62,279 hospitalized SARS-CoV-2 positive patients. They investigated factors associated with either discharge home (-/+ Mortality), or to a inpatient post acute setting (-/+ death) and those that died in hospital.

They found that discharge to PAC and in hospital death was associated with older age, higher EI, along with elevated CRP and D-dimer levels (factors associated with worse outcome in SARS-CoV-2 infection) compared to those that were discharged home.

I was invited as an additional reviewer and I was unable to see the tracked changes version of the manuscript, so I cannot comment on how the manuscript has changed since the previous version.

I may have missed something, but cannot see any mention of influenza patients and discharge to PAC or home, given that in the discussion the authors state that they wanted to investigate differences in PAC utilization.

The authors state that D-dimer is an inflammatory marker. D-dimer is a marker of coagulation activation and not inflammation, this needs to be clarified in the text.

Table 2 + 3 need to define cut-off values for "high, low and normal" for haemoglobin, WBC and plts.

Include units within the tables.

Reviewer #4: It is a very well written article. I do not have much comments in terms of improving the quality of the article.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: No

Reviewer #4: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Decision Letter 2

Robert Jeenchen Chen

7 Feb 2023

PONE-D-21-40001R2Predictors of Discharge Disposition and Mortality following Hospitalization with SARS-CoV-2 InfectionPLOS ONE

Dear Dr. IKRAMUDDIN,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please revise.

Please submit your revised manuscript by Mar 24 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: (No Response)

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

Reviewer #4: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: I thank the authors for addressing my comments and the manuscript is much improved.

Minor point

Could the authors please standardize how they state “d-dimer”. It changes throughout the manuscript; “D-dimer, d-dimer, D dimer, D-DIMER, DDIMER”.

Reviewer #4: It is a very well written article. I do not have much comments in terms of improving the quality of the article.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: No

Reviewer #4: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Decision Letter 3

Robert Jeenchen Chen

7 Mar 2023

Predictors of Discharge Disposition and Mortality following Hospitalization with SARS-CoV-2 Infection

PONE-D-21-40001R3

Dear Dr. IKRAMUDDIN,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

Reviewer #4: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: (No Response)

Reviewer #4: It is a very well written article. I do not have much comments in terms of improving the quality of the article.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: No

Reviewer #4: No

**********

Acceptance letter

Robert Jeenchen Chen

3 Apr 2023

PONE-D-21-40001R3

Predictors of Discharge Disposition and Mortality following Hospitalization with SARS-CoV-2 Infection

Dear Dr. Ikramuddin:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Robert Jeenchen Chen

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. New onset SARS-COV-2 symptoms on presentation by discharge disposition using Fisher’s exact test.

    (DOCX)

    Attachment

    Submitted filename: Response to Review PLOS ONE Final (3).docx

    Attachment

    Submitted filename: Response to Reviewers PLOS ONE 2023.docx

    Attachment

    Submitted filename: Response to Reviewers 2-8-2023.docx

    Data Availability Statement

    All relevant data are within the paper and its Supporting Information files.


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